The art is replete with many references relating to drug delivery systems that when orally administered are retained in the stomach. Several such systems disclosed in prior art relate to retention of system in the stomach because the size of the system is large and thereby gastric emptying is delayed.
Prior art systems that provide a control on the release of the drug and also are retained in stomach because of their size and shape have certain drawbacks. The major drawback of a large majority of the disclosed prior art systems that have become commercially useful is that they are not sufficiently large in size initially but attain their size by swelling to several times their initial size this entails a risk that the system would be emptied from the stomach before it swells. This drawback has been overcome to an extent by systems that swell rapidly, however such systems must include enough quantities of swelling agents that swell rapidly but despite the internal swelling pressure created must not disintegrate earlier than desired. These requirements make the formulator's task difficult. There may be further limitations in formulation options for the formulator because the drug-containing matrix should release drug at a desired controlled release rate while also retaining its size. For example, this may be difficult when the dose of the active ingredient is large and relatively smaller quantities of pharmaceutical excipients suffice to provide the controlled release. A matrix so formed containing higher proportions of active ingredients as compared to other pharmaceutical excipients often erodes or disintegrates into parts earlier than desired for gastric retention. For example, systems disclosed in U.S. Pat. No. 4,777,033 (Patent '033) were found to have a drawback in that they did not remain intact when subjected to agitation in an aqueous medium. On the other hand, systems that are designed to avoid erosion or disintegration may be eliminated in the stools in an intact form, which raises apprehensions in the patient about the quality of the tablets or that he did not absorb the active ingredient.
There remains a need for a drug delivery system that provides an independent controlling mechanism for providing a slow delivery of the active ingredient and an independent controlling mechanism for providing size and rigidity and retaining size so as to be retained in the stomach over the desired period of release and which system is completely eroded or disintegrated in the intestine.
We described a novel drug delivery system in WO 2005/039481 (herein after referred to as '481publication), now U.S. application Ser. No. 10/572,502 published as US 2007/0071816 on Mar. 29, 2007, which is incorporated herein by reference. This patent application describes a novel oral drug delivery system that comprises a core with drug composition and a coating surrounding said core. In one embodiment, the coated tablet was designed to include a design feature comprising a swellable composition adjacent to a preselected surface of the coating. On imbibing water, the swellable composition swells and exerts pressure on the coating, particularly at the preselected surface, and the coating from only that preselected surface is removed. At the same time, the coating maintains its physical form and rigidity on other surfaces of the system to form a cup-shaped platform. The system was designed such that coating from one or more of the preselected surfaces was removed, and drug release occurred from the exposed surface. The exposed surface area remains constant over the periods of release and the drug was released at a uniform or zero-order rate from the system.
However, we have found that the oral drug delivery system of '481 can be modified to provide systems of the present invention in the form of coated tablets that are suitable for gastric retention and overcome the aforesaid drawbacks of the prior art gastric retention systems. The coated tablets of the present invention have an initial size and rigidity that is retained at least along one dimensions of the tablets and along at least one more dimension the size and rigidity is retained partially when the tablets are subjected to agitation in an aqueous medium. In other words, at least along one dimension the original size is retained and along a second dimension the size decreases as the components of the coated tablets erode or dissolve until an intermediate size is achieved and thereafter the coated tablets do not substantially erode or dissolve in the gastric fluids. The intermediated size tablet remnant can be emptied from the stomach without gastric obstruction, and in the intestine it can disintegrate or erode or dissolve.